A NICHE
MARKET-LEVOTHYROXINE
TABLET
May 2004

Innovative Companies Inc. (GORX) filed a patent application on a novel method to
stabilize the drug levothyroxine on January 12, 2004.  Levothyroxine sold in oral tablet
dosage form is used to treat thyroid-related conditions. The major players in the
manufacturing of levothyroxine tablets include Abbott, Alara Pharm, GenPharm, Jones
Pharma, Lloyd, Mylan, Stevens J and Vintage Pharms (Table 1). The retail sales for all
levothyroine sodium tablets were about $1.1 billion in 2002. However, levothyroxine
sodium is hygroscopic and degrades rapidly under conditions of high humidity or
light. Though a few patents for stabilizing levothyroxine have been filed and issued
(Attachment 1), instability with the commerical products still occasionally occured in
the last four years (Table 2).

Since there is a stabiity problem associated with the active ingredient and there are
already a few patents issued for the stabilization methods, it represents a barrier for
most generic companies without an unique/non-infringing technology get into this
market.

                                             
                                   
   TABLE 1
                       MAJOR PLAYERS IN THIS AREA

ABBOTT-----------SYNTHROID (BX) ----------------------------------------Oral Tablets
Alara Pharm-------Levo-T (BX) ----------------------------------------------Oral Tablets
GenPharm---------Novothyrox (BX)------------------------------------------Oral Tablets
Jones Pharma-----Levoxyl (BX) ---------------------------------------------Oral Tablets
Lloyd----------------Thyro-Tabs (BX) ----------------------------------------Oral Tablets
Mylan----------------Levothyroxine Sodium Tablet (AB)------------------Oral Tablets
Stevens J.----------Levothyroxine Sodium Tablet (AB)------------------Oral Tablets
Vintage Pharms --Levolet (BX)----------------------------------------------Oral Tablets

                                             
TABLE 2
RECALLS (1999-2004) RELATED TO SUBPOTENCY/STABILITY ISSUES

DATE                      PRODUCTS                                   COMPANY
July 25, 2001               Levothyroxine                     Vintage Pharmaceuticals, Inc.
                      sodium tablets
October 17, 2001             Levoxyl                           King Pharmaceuticals, Inc.
December 29, 1999       Levothroid                         Forest Pharmaceuticals, Inc.
April 17, 2002              Levothyroxine                      Vintage Pharmaceuticals, Inc.

                                     
ATTACHMENT 1
PATENTED METHODS FOR LEVOTHYROXINE STABILIZATION

Methods used to stabilize levothyroxine in medications have been studied more than
a decade. The leading group in this area is Chen et al (US Patent 5,225,204, July 6,
1993). They stabilized levothyroxine sodium by complex formation using
polyvinylpyrrolidone. Later, Groenewoud et al (US Patents 5,635,209 and 6,190,696
Vintage Pharmaceuticals, Inc.) stabilized levothyroxine sodium using iodide as a
stabilizing excipient. Mitra et al (US Patents 5,955,105 and 6,056,975) stabilized the
compound with a mixture of glycine, a carbohydrate and an inorganic salt. Frontanes,
et al (US Patent 6,399,101) used silicified microcrystalline cellulose to stabilize the
drug. Schreder, et al (US Patent 6,491,946) used a mixture of potassium iodide,
microcrystalline cellulose and binding agent to prepare a stable preparation of
levothyroxine. While, Franz et al (US Patent 6,555,581, Jones Pharma Inc.) prepared a
stable composition using beta-form of microcrystalline cellulose and disintegrant

HOME
PHARMCEUTICAL
INDUSTRY

Foundamental
Science
Colloidal
Stabilization

Drug Product
Development
Patent Application
Product
Development
Product
Ingredients
Colorant
Scale up a batch 1
Drug Delivery
Industry
Drug Delivery -
Smart Bomb
Lotion, Cream,
Preps
Enteric
Coating-Eudragit
Enteric
Coating-Nutrateric
SR
Coating-Aquacoat

Drug Industry
Drug
Competitions
Drug in
Development
Cholesterol-lowering
Drug-Terminologies
Packaging
Materials

Market
Drug Dev- 2004
Drug Dev -
2005Q1
Drug Dev- 2005Q2
Drug
Dev-2005Summer
Drug Dev-2005Q3
Orphan Drug
Protein Drug
Niche Market

Novo Norkdisk
R&D

Equipment
Blenders

CONTRACT
MANUFACT.
Nutrition
Supplements

NEW DRUGS
Arranon
Actoplus Met
Alfuzosin
Ambien CR
Avastin
Asmanex(R)
Erbitux
(cetuximab)
Gardasil
GRN163
Herceptin
Increlex (rhIGF-1)
Lidoerm
(Lidocaine)
Liraglutide
Lyrica (pregabalin)
Rozerem
Sorafenib
Sutent
Tamsulosin
Torcetrapib
Zometa
OLD DRUGS
Lithium Carbonate
DRUG NOTES
[CONSTRUCT]
Clinical Research
Terminologies
FDA ALERTS
Protein Drug
Market
Niche Market
Orphan Drug
levothyroxine
Protein Drug 1
Protein Drug2

Double-blind
Study